Patients undergoing open heart surgery have the pumping functions of the heart and the gas exchange functions of the lungs temporarily replaced by various apparatus in an external (extracorporeal) circuit. In the last 30 years, technological advances related to the components of these extracorporeal systems have provided significant benefits to these patients. For example, completely disposable components of an extracorporeal circuit and associated blood-contacting surfaces have been fabricated, which eliminate adverse patient reactions due to contamination from trace amounts of a previous patient's blood supply.
During a typical operation requiring extracorporeal circulation, blood from the cardiovascular system of the patient is typically taken from the patient and delivered through tubing to an oxygenator which serves as an external lung. Within the oxygenator, blood is exposed to an appropriate percentage of oxygen and carbon dioxide. The perfusate is drawn from the oxygenator by an arterial pump and delivered to a blood filter, which removes gaseous microemboli, fat emboli, aggregates and microaggregates, and other debris. From the filter, the blood is usually returned directly to the vascular system of the patient. Ancillary circuits, typically including one to three additional pumps and a small reservoir, may be used to salvage blood from the operative site. The salvaged blood is delivered to a cardiotomy reservoir where it can be filtered and stored until the surgeon returns the blood directly or indirectly through the oxygenator to the patient's cardiovascular system. By these means, the requirement for external blood replacement is often minimized.
The technological improvements noted above have focused on minimizing red cell damage in both the main circuit, comprising the oxygenator, arterial pump, and filter, and the ancillary blood salvage circuits. However, the presence of these devices, which are necessary for the transport and gas exchange of the blood but nonetheless are foreign to the patient's body, may have a deleterious effect on leucocytes, or white blood cells, in the blood. Contact between the internal surfaces of these foreign devices and the leucocytes may elicit an immune response and/or may result in the formation and release of a host of toxic mediators, and what is commonly referred to as oxygen-free radicals.
Leucocytes are a type of blood cell in the immune system which constitute the principal means of defense against antigens, such as infection by pathogenic microorganisms and viruses, and probably also against most cells that undergo transformation into cancer cells. Leucocyte activation, the leucocytic monitoring and arming functions, proceeds from a complex series of biochemical interactions, typically terminating in engulfing and digesting the antigen. If the leucocytes have been so activated, but lack an appropriate antigenic target, the leucocytes may inflict damage to internal organs, particularly ischemic tissues, i.e., tissues in which no blood is flowing such as the heart and lungs during certain surgical procedures. This effect, called "reperfusion injury", is well known and is commonly caused by leucocyte activation as a result of leucocyte contact with foreign matter such as the large internal surface area of an extracorporeal circuit.
The activated leucocytes associated with reperfusion injury release both proteolytic enzymes, which may lead to the destruction of cellular function and structure, and oxygen metabolites ("free radicals") which could lead to death. Extracorporeal circuit-induced activated leucocytes have been implicated in microcirculatory stasis, leucocyte sequestration, vasospasm, organ destruction, interstitial edema, microvascular occlusion (including myofibrillar necrosis, mitochondrial disruption, and nuclear chromatin clumping), lung endothelium damage, and the release of chemotactic factors.
Leucocytes have also been implicated as the singular cause or a major contributory factor in a growing number of transfusion complications, including non-hemolytic febrile reactions, alloimmunization, viral transmission (e.g., Cytomegalovirus, Human T-cell Lymphotropic Virus Type I), immune suppression and modulation, graft versus host reactivity, and refractoriness to platelets. Moreover, with increasing frequency, the most common leucocyte, the granulocytic neutrophil, has been implicated as the mediator of tissue destructive events in a variety of disorders, including reperfusion injury, respiratory distress syndromes, rheumatoid arthritis, skin disorders and ulcerative colitis. The commonality which pervades these pathologies is the neutrophil's ability to release a number of agents which can disrupt and destroy normal cellular function, dissolve connective tissue, and cause injury to organs.
It has also been shown that circulating leucocytes contribute to or mediate ischemic and reperfusion injury during organ preservation, particularly following extended preservation of the heart-lung bloc commonly required during cardiopulmonary bypass operations (CPB). Leucocytes have also been associated with increased oxygen radical activity, pulmonary edema, and vasoconstriction.